PROJECT SUMMARY/ABSTRACT Chronic tics affect 1-3% of youth in the US and are a disabling neuropsychiatric symptom associated with multiple childhood-onset mental disorders. Tic suppression using Comprehensive Behavioral Intervention for Tics (CBIT) is the current first-line, gold-standard therapy for tics. However, many patients do not fully benefit from CBIT, likely because they lack the fundamental tic suppression ability that CBIT aspires to enhance. Our preliminary data and the literature show that tic suppression ability can be enhanced with inhibitory repetitive transcranial magnetic stimulation (rTMS) of the supplementary motor area (SMA). SMA is a key node of cortico-striatal circuits and is known to be hyperactive and hyperconnected in tic disorders. We therefore anticipate that combining CBIT with inhibitory stimulation of SMA may facilitate higher CBIT response rates. This study will test whether augmenting CBIT with inhibitory, noninvasive stimulation of SMA normalizes activity in SMA-mediated circuits and enhances tic suppression ability in young people with tic disorder. The R61 phase will compare two rTMS regimens, 1 Hz rTMS and continuous theta burst stimulation (cTBS), against sham stimulation. R61 aims will test engagement of brain (SMA-mediated circuits) and behavior (tic suppression ability) targets and identify the optimal rTMS regimen. To this end, 60 youth ages 12-21 years with chronic tics will complete 10 daily sessions of CBIT plus randomly assigned rTMS regimen, with fMRI, behavioral, and clinical assessments before and after treatment. The R33 phase will investigate the effects of CBIT augmentation with the optimal rTMS regimen in a double blinded randomized control trial in a new sample of 60 youth with chronic tics. R33 aims test the link between target engagement and functional outcomes, examine the clinical trajectory of the dose-response relationship, and assess intervention durability at 1 month follow-up. TMS targeting in both phases will be informed by individualized electric field modeling. This project will establish CBIT+rTMS as a treatment for chronic tics and provide a model for mechanistically studying pediatric interventions combining behavior therapy with neurostimulation. Results from this line of research will inform TMS therapy augmentation strategies and improve our understanding of neural mechanisms underlying CBIT, TMS, and tics.